title: Brainstem structures are primarily affected in an experimental model of severe scorpion envenomation.
abstract: Severe scorpion envenoming (SSE) is more frequent in children and is characterized by systemic dysfunctions with a mortality rate of up to 9%. Recent evidence shows that the central nervous system (CNS) plays a key role in triggering the cascade of symptoms present in SSE. The age-dependent role of the CNS in SSE lethality may be summarized in 3 hypotheses: (1) the shown increased blood brain barrier permeability of infants to the toxins would especially and primarily compromise neurovegetative control areas, (2) the neurons within these areas have high affinity to the toxins, and (3) the neurovascular interaction is such that SSE metabolically compromises proper function of toxin-targeted areas. A pharmacological magnetic resonance imaging paradigm was used to evaluate localized hemodynamic changes in relative cerebral blood volume (rCBV) for 30 min after the injection of TsTX, the most lethal toxin from the venom of the Tityus serrulatus scorpion. The brainstem showed significant rCBV reduction 1 min after TsTX administration, whereas rostral brain areas had delayed increase in rCBV (confirmed by laser Doppler measurements of cortical cerebral blood flow). Moreover, metabolic activity by 14C-2-deoxyglucose autoradiography showed the highest relative increase at the brainstem. To test whether TsTX has high affinity to brainstem neurons, the lateral ventricle was injected with Alexa Fluor 568 TsTX. Although some neurons showed intense fluorescence, the labeling pattern suggests that specific neurons were targeted. Altogether, these results suggest that brainstem areas involved in neurovegetative control are most likely within the primary structures triggering the cascade of symptoms present in SSE.
authors.affiliation: * Núcleo de Neurociências (NNC), Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas and.
authors.forename: Patrícia Alves Maia
authors.initials: PA
authors.lastname: Guidine
authors.forename: Diana
authors.initials: D
authors.lastname: Cash
authors.forename: Luciana Estefani
authors.initials: LE
authors.lastname: Drumond
authors.forename: Gustavo Henrique
authors.initials: GH
authors.lastname: de Souza E Rezende
authors.forename: André Ricardo
authors.initials: AR
authors.lastname: Massensini
authors.forename: Steve Charles Rees
authors.initials: SC
authors.lastname: Williams
authors.forename: Tasso
authors.initials: T
authors.lastname: Moraes-Santos
authors.forename: Márcio Flávio Dutra
authors.initials: MF
authors.lastname: Moraes
authors.forename: Michel Bernanos Soares
authors.initials: MB
authors.lastname: Mesquita
mesh_terms: D000367:Age Factors; D000818:Animals; D001783:Blood Flow Velocity; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001933:Brain Stem / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D017078:Laser-Doppler Flowmetry; D008279:Magnetic Resonance Imaging; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D065008:Scorpion Stings / Q000473:pathology*; D012604:Scorpion Venoms / Q000633:toxicity*; D012605:Scorpions; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D012604:Scorpion Venoms; D003847:Deoxyglucose
keywords: cerebral blood flow.; encephalic perfusion; glucose utilization; scorpion envenoming